While the idea that "exercise is good for children" seems axiomatic, translating this vague notion into specific, guidelines that actually influence health has proved to be difficult. With the alarming increase in obesity, type 2 diabetes, and metabolic syndrome in children, as well as the growing number of childhood survivors of disease and disability, never before has the need for such guidelines been so great. This Program is built on recent exciting discoveries, preliminary studies, and technological advances leading to a "phase shift" in identifying potential novel mechanisms linking exercise and health in the growing child. The objectives of this Program are: 1) To investigate how exercise paradoxically alters growth mediators, stress/inflammatory factors, and related elements of oxidative stress in a manner that can influence health in babies and children; 2) To determine how these exercise factors are altered by gender and maturational status and their impact during "critical periods" of growth and development when factors like physical activity affect health not only in the short term but for the life of the organism; 3) To create a scientific environment designed to link basic scientific discoveries to clinical relevancy. The 4 Projects that make up this Program are designed to: 1) examine molecular mechanisms that link stress/inflammatory and growth factor responses to exercise in muscle using the rat model; 2) discover how exercise stimulates gene regulation and intracellular production of stress/inflammatory and growth factors in peripheral blood mononuclear cells in children; 3) explore the impact of exercise associated production of reactive oxygen species on stress/inflammatory and growth factors in healthy children and in children with metabolic syndrome; and 4) determine how assisted exercise in premature babies alters stress/inflammatory and growth factors and improves weight gain and muscle mass early in life. The research will be supported by an Administrative Core which will promote scientific interaction among the Projects, facilitate subject recruitment and regulatory complicance, and provide statistical expertise; and a Pediatric Growth, Stress, and Inflammatory Mediator Core Laboratory which will handle the bulk of samples derived from the 4 projects and interface with other central laboratories (e.g., gene microarray, flow cytometry, breath biomarker) to ensure optimal and efficient use of these resources. The synergy of basic and clinical research will help define a set of biological mechanisms that can be used to determine an optimal, health-enhancing balance of pro- and anti-inflammatory, catabolic and anabolic effects of exercise in healthy children and in children with chronic disease and disability.